Evidence from inflammatory bowel diseases (IBD) patients and animal models has indicated that gut inflammation is driven by effector CD4⁺ T-cell, including Th1 and Th17. Conversely, Treg seem to be dysfunctional in IBD. Importantly, dopamine, which is abundant in the gut mucosa under homoeostasis, undergoes a sharp reduction upon intestinal inflammation. Here we analysed the role of the high-affinity dopamine receptor D3 (DRD3) in gut inflammation. Our results show that Drd3 deficiency confers a stronger immunosuppressive potency to Treg, attenuating inflammatory colitis manifestation in mice. Mechanistic analyses indicated that DRD3-signalling attenuates IL-10 production and limits the acquisition of gut-tropism. Accordingly, the ex vivo transduction of wild-type Treg with a siRNA for Drd3 induced a potent therapeutic effect abolishing gut inflammation. Thus, our findings show DRD3-signalling as a major regulator of Treg upon gut inflammation.

来自炎症性肠病 (IBD) 患者和动物模型的证据表明，肠道炎症是由效应 CD4 ⁺ T 细胞驱动的，包括 Th1 和 Th17。相反，Treg 在 IBD 中似乎功能失调。重要的是，在体内平衡下肠道粘膜中富含的多巴胺会在肠道炎症时急剧减少。在这里，我们分析了高亲和力多巴胺受体 D3 (DRD3) 在肠道炎症中的作用。我们的结果表明Drd3缺乏赋予 Treg 更强的免疫抑制效力，减轻小鼠的炎症性结肠炎表现。机制分析表明 DRD3 信号减弱了 IL-10 的产生并限制了肠道趋向性的获得。因此，用Drd3的 siRNA 离体转导野生型 Treg诱导了消除肠道炎症的有效治疗效果。因此，我们的研究结果表明 DRD3 信号是 Treg 对肠道炎症的主要调节因子。